Clinical implications of additional posterior fractures in combined anterior-posterior pelvic ring fractures in elderly patients

ObjectivesHistorically, pelvic ring fractures (PRF) are considered to occur predominantly in the anterior ring and therfore to be mechanically stable. Combined anterior and posterior (A + P) PRF are expected to be less mechanically stable and therefore to be associated with higher levels of pain and reduced mobility compared to isolated anterior fractures. The current study investigates the clinical relevance of combined A + P PRF in elderly patients.MethodsA prospective multicentre cohort study was conducted in patients >70 years of age with anterior PRF after low-energy trauma diagnosed on conventional radiographs. All patients underwent an additional CT-scan. Patients were divided into two groups; isolated anterior or combined A + P fractures. Patients were treated conservatively with adequate analgesia for at least one week. If patients could not be mobilised after conservative treatment, surgical fixation was performed. Numerical Rating Scale (NRS) pain scores, dependence on walking aids and Activities of Daily Living scores (ADL) were measured at 2–4 weeks, and 3, 6 and 12 months after fracture.Results102 patients (age 81.1 ± 7.6 years) were included. Isolated anterior fractures were diagnosed in 25 (24.5%) and A + P fractures in 77 (75.5%) patients. Baseline characteristics did not differ between the two groups. Most patients were successfully treated conservatively and 5 (4.9%) underwent percutaneous trans-iliac, trans-sacral screw fixation after failure of conservative treatment. At 2–4 weeks post trauma, patients with A + P fractures had similar median pain scores (3 (range 0–8) vs. 5 (0–10), p = 0.19) and ADL scores (85 (25–100) vs. 78.6 (5–100), p = 0.67), but were more dependent on walking aids (92.8% vs. 72.2%; p = 0.02) compared to patients with isolated anterior fractures. There were no significant differences at 3 months. At one year follow-up the median NRS pain and ADL scores for both fracture groups were 0 and 100, respectively. Mortality was 10.8%, and additional loss to follow-up was 17.6%.ConclusionsThe vast majority of elderly patients with PRF have combined A + P fractures. The clinical implications of additional posterior pelvic ring fractures in elderly patients appears to be limited.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.     

Semi-perfusion cultures of suspension MDCK cells enable high cell concentrations and efficient influenza A virus production

Control and prevention of rapid influenza spread among humans depend on the availability of efficient and safe seasonal and pandemic vaccines, made primarily from inactivated influenza virus particles. Current influenza virus production processes rely heavily on embryonated chicken eggs or on cell culture as substrate for virus propagation. Today’s efforts towards process intensification in animal cell culture could innovate viral vaccine manufacturing using high-yield suspension cells in high cell density perfusion processes. In this work, we present a MDCK cell line adapted to grow as single cell suspension with a doubling time of less than 20 h, achieving cell concentrations over 1 × 10⁷ cells/mL in batch mode. Influenza A virus titer obtained in batch infections were 3.6 log₁₀(HAU/100 µL) for total- and 10⁹ virions/mL for infectious virus particles (TCID₅₀), respectively. In semi-perfusion mode concentrations up to 6 × 10⁷ cells/mL, accumulated virus titer of 4.5 log₁₀(HAU/100 µL) and infectious titer of almost 10¹⁰ virions/mL (TCID₅₀) were possible. This exceeds results reported previously for cell culture-based influenza virus propagation by far and suggests perfusion cultures as the preferred method in viral vaccine manufacturing.     

两种补肾方药对骨质疏松症患者骨密度及疼痛评分影响的Meta分析

目的:系统评价并对比以金匮肾气丸为主的补肾方药与以六味地黄丸为主的补肾方药在治疗骨质疏松症的临床疗效。方法:计算机检索SCI、PubMed、中国期刊全文数据库(CNKI)、Cochrane图书馆、EMbase、万方等各类中、英文数据库,检索年限截止至2019年3月,检索有关补肾方药治疗骨质疏松症的随机对照文献(Randomized Controlled Trial,RCTs)。采用RevMan 5.3软件进行数据的Meta分析。结果:纳入5项RCT分为两组(一组2项,一组3项),涉及受试者421例,Meta分析结果显示,在骨密度(Bone Mineral Density,BMD)方面:以金匮肾气丸为主的补肾方药,治疗组优于对照组最为明显(MD=-2.13,95%CI为-3.00^-1.26,P<0.00001);在视觉模拟疼痛评分(Visual Analogue Scale,VAS)方面:以金匮肾气丸为主的补肾方药,治疗组优于对照组最为明显(MD=0.03,95%CI为-0.01~0.06,P=0.10)。结论:以金匮肾气丸为主的补肾方药在治疗骨质疏松症的临床疗效比以六味地黄丸为主的补肾方药积极意义更高。     

Expression of Salivary S100A7 Levels in Stage I Oral Submucous Fibrosis: A Clinical and Laboratory Study

Background: Oral submucous fibrosis (OSF) is a chronic debilitating condition characterized by juxta-epithelial fibrosis. The main etiological agent associated with the high-risk precancerous condition is areca nut use. S100A7 is a member of the largest calcium-binding proteins exclusively found in vertebrates and are associated with the regulation of numerous intracellular and extracellular functions. The aim of this study was to investigate the expression of protein S100A7 in salivary samples of individuals with stage I OSF and healthy controls. Methods: This study included 63 participants, 30 of whom had OSF stage I and 33 healthy controls. Nonprobability quota sampling technique was utilized for recruitment of the study participants. A structured baseline questionnaire was used to collect demographic data. Saliva samples were collected by passive droll technique in a sterile container. Salivary levels of S100A7 were quantified by enzyme-linked immunosorbent assay. For the normality of the data Shapiro Wilk test was performed. Student t-test was commuted to evaluate the expression of S100A7 protein expression between both the study groups. Results: The mean salivary S100A7 value for stage I OSF group was 0.334 ng/ml, compared to 0.172 ng/ml for healthy controls. Student t-test reported a statistically significant difference, indicating higher levels of S100A7 in stage I OSF group than in healthy controls (p < 0.001). In the individual group analysis, a significant negative correlation was found between salivary S100A7 and duration of areca nut use (r = –0.45, p = 0.009) and gutka chewing (r = –0.20, p = 0.03), while a significant positive correlation was found between salivary S100A7 and mouth opening (r = 0.03, p = 0.04). Conclusions: Higher levels of S100A7 protein level was seen in stage I OSF group in comparison to the healthy individuals. Results of our study suggest that S100A7 could be used as a surrogate assessment to identify patients at risk of OSF development.     

维生素A对糖基化终末产物诱导的角膜上皮细胞损伤的作用及机制研究

目的糖基化终末产物(AGEs)在糖尿病患者在角膜外伤或接受角膜手术时极易出现角膜上皮愈合延迟甚至不愈的过程中起着关键作用,本文研究维生素A(VA)对以糖基化终末产物AGE-BSA诱导角膜上皮细胞损伤的影响及可能的作用机制。方法以HCE-2细胞为研究对象,AGE-BSA为诱导剂,试剂盒检测VA对细胞凋亡率及线粒体膜电位的影响,荧光显微镜检测细胞内凋亡小体,Western blot检测相关的蛋白表达量。结果VA抑制AGE-BSA诱导的HCE细胞凋亡,调节AGEBSA引起的凋亡相关蛋白的变化。同时,VA与JNK的抑制剂同等程度的减少AGE-BSA诱导的JNK和NF-κB的磷酸化。结论VA可能通过抑制JNK介导的NF-κB炎症通路而起到减少AGE-BSA诱导的角膜上皮细胞凋亡的作用,可以作为糖尿病患者角膜上皮损伤的保护剂。